PP-10 Phenotypic manifestations of copy number variation in chromosome 11p11.2-p11.12

Objective

Advanced maternal age pregnancies are an increasing incidence, especially in developed countries. As the age of conception increases, the risk of chromosomal anomalies and genetic diseases also increases. Detection of chromosomal anomalies such as deletion, microdeletion or duplication-microcopying has become possible with developing technology and increasing clinical applications such as new generation sequencing analysis and chromosomal microarray analysis.[1] Chromosome 11 encompasses approximately 135 million DNA building blocks and contains approximately 1300-1400 protein-coding genes.[2] These proteins perform various functions in the body. Changes in the structure or copy number of the 11th chromosome lead to different clinical pictures. The common features of previous cases in this extremely rare chromosomal anomaly are autism, mental and motor retardation, growth retardation, polyhydramnios, dysmorphic findings, hypotonia, and macrosomia.[1,3] 

Methods

The computer-based and ultrasonography records of the case, who applied to the Perinatology outpatient clinic of Prof. Dr. Cemil Taşçıoğlu City Hospital at the 13th week of pregnancy, had NIPT due to advanced maternal age and the result was reported as multiple chromosomal anomaly, were analyzed retrospectively from the hospital system and the history of the ultrasonography device. Fetal ultrasonography examination was performed using Mindray Resona 7 device and its 1.2-6 MHz convex abdominal probe. Ultrasonography findings and patient history were noted.

Case

41-year-old patient with gravida 2, parity 1 applied to our clinic for the first trimester screening test. In the anamnesis taken from the patient, it was learned that she had a history of cranial hemorrhage due to methyl alcohol poisoning 6 years ago, that she had vision loss at a rate of 60%, and that she continued to use alcohol regularly throughout her pregnancy. Non-invasive prenatal testing (NIPT) was recommended to the patient due to advanced maternal age, and a cystic lesion of approximately 5 cm in the left ovary was observed in the left ovary, which was compatible with endometrioma. Amniocentesis was recommended to the patient after NIPT revealed multiple chromosomal anomaly. Amniocentesis was performed on the patient at the 20th week of her pregnancy. In the ultrasonography performed at the 20th gestational week, the fetus was measured as compatible with 22 weeks. Macrosomia, macrocephaly and polyhydramnios were present. TORCH and OGTT test results were normal. Genetic analysis was requested from the parents after the fetus with a normal karyotype result was found to have a 2.65 Mb (303 probe) copy number variation (CNV) increase in the 11p11.2-p11.12 region of 11p11.2p11.12(47814450_50468342)x3 case in array CGH.
After the parents’ genetic tests were reported as normal, de-novo mutation was considered and genetic counseling was given to the patient. During this period, all fetal biometric measurements continued as >97th percentile. Fetocyte and termination procedure was performed at the 32nd week of pregnancy with the decision of the pregnant woman and her husband, after the findings of macrosomia, macrocephaly and polyhydramnios were accompanied by ultrasound, regular alcohol use throughout the pregnancy and the presence of 2.65 Mb CNV in the 11th chromosome. On the 1st day after termination, the patient was discharged without any complaints.

Results

In patients with advanced maternal age risk factors, first trimester combined screening test and antenatal screening tests, especially NIPT, are of great importance in determining the risk of fetal chromosomal anomalies. Multidisciplinary management of rare chromosomal anomalies such as the case we have presented, together with Medical Genetics, provides detailed information to families. The increasing complexity of genetic counseling as a result of advanced genetic studies can be overcome by joint studies between branches.

Keywords

Microarray, chromosomal anomaly, NIPT, fetal anomaly, prenatal screening tests.

1. Chen X, Xu H, Shi W, Wang F, Xu F, Zhang Y, et al. 11p11.12p12 duplication in a family with intellectual disability and craniofacial anomalies. BMC medical genomics. 2021 Apr 9;14(1):99. 
2. Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, Dewar K, et al. Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature. 2006 Mar;440(7083):497–500.
3. Montgomery ND, Turcott CM, Tepperberg JH, McDonald MT, Aylsworth AS. A 137-kb deletion within the Potocki-Shaffer syndrome interval on chromosome 11p11.2 associated with developmental delay and hypotonia. American Journal of Medical Genetics Part A. 2012 Dec 13;161(1):198–202.